MAPK10

mitogen-activated protein kinase 10, the group of Mitogen-activated protein kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 4:85990006-86594625

Previous symbols: [ "PRKM10" ]

Links

ENSG00000109339 ∙ NCBI:5602 ∙ OMIM:602897 ∙ HGNC:6872 ∙ Uniprot:P53779 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lennox-Gastaut syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epileptic encephalopathy, Lennox-Gastaut type	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16249883; 23329067
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAPK10 gene.

• not provided (62 variants)
• Inborn genetic diseases (23 variants)
• not specified (4 variants)
• Epileptic encephalopathy (3 variants)
• ARHGAP24-related condition (2 variants)
• Epileptic encephalopathy with cognitive deficit (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	3	7
missense			3			3
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			41	18	11	70
Total	0	0	45	22	14

Variants in MAPK10

This is a list of pathogenic ClinVar variants found in the MAPK10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-85994441-T-C			Benign (Jun 25, 2020)
4-85994529-G-T			Likely benign (Apr 06, 2020)
4-85994554-A-G			Benign (Dec 25, 2019)
4-85994606-A-G			Uncertain significance (Jun 26, 2022)
4-85994618-A-G			Uncertain significance (Oct 01, 2016)
4-85994679-G-A		ARHGAP24-related disorder	Likely benign (Jul 07, 2023)
4-85994693-A-G		ARHGAP24-related disorder	Uncertain significance (Sep 20, 2023)
4-85994695-T-C			Benign (Jan 31, 2024)
4-85994719-G-A			Conflicting classifications of pathogenicity (Jan 02, 2024)
4-85994730-A-G		ARHGAP24-related disorder	Benign/Likely benign (Dec 14, 2023)
4-85994761-C-G			Uncertain significance (Sep 12, 2022)
4-85994770-G-A			Benign (Jan 31, 2024)
4-85994812-C-T			Likely benign (Dec 23, 2022)
4-85994814-T-C		not specified	Uncertain significance (Dec 06, 2022)
4-85994815-G-A		not specified	Conflicting classifications of pathogenicity (May 05, 2023)
4-85994844-G-A			Likely benign (Oct 11, 2023)
4-85994876-C-T			Uncertain significance (Feb 20, 2022)
4-85994899-C-A		not specified	Uncertain significance (Apr 28, 2023)
4-85994903-C-G			Benign/Likely benign (Jan 30, 2024)
4-85994904-C-T		not specified	Conflicting classifications of pathogenicity (Mar 01, 2023)
4-85994912-G-A			Uncertain significance (Mar 03, 2023)
4-85994960-G-A		not specified	Uncertain significance (Oct 26, 2021)
4-85994969-A-G		not specified	Uncertain significance (Nov 08, 2022)
4-85994972-A-C		not specified	Uncertain significance (Dec 07, 2021)
4-85994988-G-A			Uncertain significance (Oct 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPK10	protein_coding	protein_coding	ENST00000359221	12	579009

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.276	0.724	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.04	121	259	0.468	0.0000132	3076
Missense in Polyphen		22	90.659	0.24267		1105
Synonymous	0.227	92	94.8	0.970	0.00000515	835
Loss of Function	3.57	6	25.4	0.236	0.00000114	327

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000308	0.000308
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress- activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22441692}.
• Disease: DISEASE: Note=A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation. {ECO:0000269|PubMed:16249883}.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Tight junction - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);VEGF Signaling Pathway;EGF-Core;Regulation of toll-like receptor signaling pathway;Integrin-mediated Cell Adhesion;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Apoptosis;Focal Adhesion;Apoptotic Signaling Pathway;MAPK Signaling Pathway;Apoptosis Modulation by HSP70;RIG-I-like Receptor Signaling;Angiopoietin Like Protein 8 Regulatory Pathway;Oxidative Damage;Wnt Signaling Pathway and Pluripotency;Oxidative Stress;Wnt Signaling in Kidney Disease;Chromosomal and microsatellite instability in colorectal cancer;MAPK Cascade;Ras Signaling;Insulin Signaling;G13 Signaling Pathway;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signaling by Interleukins;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;Oxidative Stress Induced Senescence;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Cellular Senescence;Fas;Cellular responses to stress;FCERI mediated MAPK activation;Fc epsilon receptor (FCERI) signaling;Innate Immune System;Immune System;IL-1 p38;IL-1 JNK;TGF-beta super family signaling pathway canonical;Cellular responses to external stimuli;IL-7 signaling;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;Activation of the AP-1 family of transcription factors;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Glucocorticoid receptor regulatory network;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;Noncanonical Wnt signaling pathway;EPO signaling;TGF-beta signaling TAK1;TLR ECSIT MEKK1 JNK;TLR JNK;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF;ErbB2/ErbB3 signaling events;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;CD40/CD40L signaling;p75(NTR)-mediated signaling;FAS (CD95) signaling pathway;FoxO family signaling;PDGFR-beta signaling pathway;Nephrin/Neph1 signaling in the kidney podocyte;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.624

Intolerance Scores

• loftool: 0.233
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.918
• hipred: Y
• hipred_score: 0.825
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mapk10
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: mapk10
• Affected structure: enteric neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: activation of MAPK activity;protein phosphorylation;signal transduction;JNK cascade;JUN phosphorylation;response to light stimulus;regulation of gene expression;intracellular signal transduction;Fc-epsilon receptor signaling pathway;regulation of circadian rhythm;rhythmic process;cellular response to organic substance
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;plasma membrane
• Molecular function: JUN kinase activity;MAP kinase activity;MAP kinase kinase activity;protein binding;ATP binding